title: Fucosylation with fucosyltransferase VI or fucosyltransferase VII improves cord blood engraftment.
abstract: OBJECTIVE
  Advantages associated with the use of cord blood (CB) transplantation include the availability of cryopreserved units, ethnic diversity and lower incidence of graft-versus-host disease compared with bone marrow or mobilized peripheral blood. However, poor engraftment remains a major obstacle. We and others have found that ex vivo fucosylation can enhance engraftment in murine models, and now ex vivo treatment of CB with fucosyltransferase (FT) VI before transplantation is under clinical evaluation (NCT01471067). However, FTVII appears to be more relevant to hematopoietic cells and may alter acceptor substrate diversity. The present study compared the ability of FTVI and FTVII to improve the rapidity, magnitude, multi-lineage and multi-tissue engraftment of human CB hematopoietic stem and progenitor cells (HSPCs) in vivo.
  
  
  METHODS
  CD34-selected CB HSPCs were treated with recombinant FTVI, FTVII or mock control and then injected into immunodeficient mice and monitored for multi-lineage and multi-tissue engraftment.
  
  
  RESULTS
  Both FTVI and FTVII fucosylated CB CD34⁺ cells in vitro, and both led to enhanced rates and magnitudes of engraftment compared with untreated CB CD34⁺ cells in vivo. Engraftment after treatment with either FT was robust at multiple time points and in multiple tissues with similar multi-lineage potential. In contrast, only FTVII was able to fucosylate T and B lymphocytes.
  
  
  CONCLUSIONS
  Although FTVI and FTVII were found to be similarly able to fucosylate and enhance the engraftment of CB CD34⁺ cells, differences in their ability to fucosylate lymphocytes may modulate graft-versus-tumor or graft-versus-host effects and may allow further optimization of CB transplantation.
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. Electronic address: snrobins@mdanderson.org.
authors.forename: Simon N
authors.initials: SN
authors.lastname: Robinson
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Thomas
authors.affiliation: Mesoblast Limited, Melbourne, Australia.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Simmons
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Junjun
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Simrit
authors.initials: S
authors.lastname: Parmar
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Shah
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martín-Antonio
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Bollard
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Gianpietro
authors.initials: G
authors.lastname: Dotti
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Savoldo
authors.affiliation: Division of Pediatrics, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Laurence J
authors.initials: LJ
authors.lastname: Cooper
authors.affiliation: Department of Experimental Imaging, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Amer
authors.initials: A
authors.lastname: Najjar
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Katayoun
authors.initials: K
authors.lastname: Rezvani
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Indreshpaul
authors.initials: I
authors.lastname: Kaur
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ian K
authors.initials: IK
authors.lastname: McNiece
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
authors.affiliation: American Stem Cell Inc, Floresville, Texas, USA.
authors.forename: Leonard P
authors.initials: LP
authors.lastname: Miller
authors.affiliation: Division of Pediatrics, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Zweidler-McKay
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects* / Q000637:transplantation; D005647:Fucosyltransferases / Q000008:administration & dosage*; D006086:Graft vs Host Disease / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D051379:Mice
chemical_list: C502597:FUT7 protein, human; D005647:Fucosyltransferases; C515956:FUT6 protein, human
keywords: FTVI; FTVII; cord blood hematopoietic stem and progenitor cells; fucosylation; improved engraftment